key: cord-0928919-xcx2euil
authors: Ali, Mohammad; Wani, Shahid Ud Din; Masoodi, Mubashir Hussain; Khan, Nisar Ahmad; Shivakumar, H. G.; Osmani, Riyaz M. Ali; Khan, Khalid Ahmed
title: nGlobal Effect of COVID-19 Pandemic on Cancer Patients and its treatment: A Systematic Review
date: 2022-04-25
journal: Clinical Complementary Medicine and Pharmacology
DOI: 10.1016/j.ccmp.2022.100041
sha: ff8ec51d81f8f42261c8af82d973e7136e3c69df
doc_id: 928919
cord_uid: xcx2euil

Background At a global level, the COVID-19 disease outbreak has had a major impact on health services and has induced disruption in routine care of health institutions, exposing cancer patients to severe risks. To provide uninterrupted tumor treatment throughout a pandemic lockdown is a major obstacle. Coronavirus disease (COVID-19) and its causative virus, SARS-CoV-2, stance considerable challenges for the management of oncology patients. COVID-19 presents particularly severe respiratory and systemic infection in aging and immunosuppressed individuals, including patients with cancer. Objective In the present review, we focused on emergent evidence from cancer sufferers that have been contaminated with COVID-19 and cancer patients who were at higher risk of severe COVID-19, and indicates that anticancer treatment may either rise COVID-19 susceptibility or have a duple therapeutic impact on cancer as well as COVID-19; moreover, how SARS-CoV-2 infection impacts cancer cells. Also, to assess the global effect of the COVID-19 disease outbreak on cancer and its treatment. Methods A literature survey was conducted using PubMed, Web of Science (WOS), Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and VIral Protein domain DataBase (VIP DB) between Dec 1, 2019 and Sept 23, 2021, for studies on anticancer treatments in patients with COVID-19. The characteristics of the patients, treatment types, mortality, and other additional outcomes were extracted and pooled for synthesis. Results This disease has a huge effect on sufferers who have cancer(s). Sufferers of COVID-19 have a greater percentage of tumor diagnoses than the rest of the population. Likewise, cancer and highest proportion is lung cancer sufferers are more susceptible to COVID-19 constriction than the rest of the population. Conclusion Sufferers who have both COVID-19 and tumor have a considerably elevated death risk than single COVID-19 positive patients overall. During the COVID-19 pandemic, there was a reduction in the screening of cancer and detection, and also deferral of routine therapies, which may contribute to an increase in cancer mortality there in future.

5 pathogenicity, COVID-19 infection causes an unregulated aberrant inflammatory reaction in some people, resulting in lung tissue harm. COVID-19 may thus pose a potential danger to cancer survivors who are receiving immunotherapy (e.g., ICIs). Patients, particularly those are receiving intensive oncologic treatment, may be among the most susceptible members of the infectious population. Just certain case studies or observational trials with scant medical data and restricted sample sizes have been conducted so far. There is a scarcity of specific evidence on tumor background, anti-tumor therapy, respiratory course, laboratory testing and death rates . Including the fact that patients undergoing successful anticancer therapy are underreported in the articles listed, people with cancer may have an increased chance of disease and serious incidents (Xiaonan et al., 2020) .

The influenced countries' oncology divisions had to change rapidly and form new organizations with a clear sense of targets. As a result, various guidelines and treatment strategies have been formulated to improve departmental structure and operation. With the purpose of offering and continuing to offer adequate treatment to every cancer sufferer. Many organizations including science associations also provided practical guidelines under these unusual situations. The first guidelines in Europe focused mostly on how to secure tumor sufferers (You et al., 2020) .

The objective of this review is to assess the global impact of COVID-19 on cancer, with an emphasis on the identification and care of COVID-19 victims, and to address strategies for treating cancer sufferers in this pandemic and to discuss how SARS-CoV-2 infection impacts on cancer.

 According to combined studies, 1-3.9 % of worldwide COVID-19 patients had tumors. Among subgroups of COVID-19 cases that became seriously sick or dead, the 7 patients more susceptible to COVID-19. Concerning tumor characteristics and active cancer treatments, utmost common primary tumor sites were lung cancer (27%), followed by colorectal (16%) and breast cancer (16%) and others as presented in the pie chart ( Fig. 1 ) (Yarza et al., 2020) . An overactive immune reaction defined as "cytokine storm" that can harm lungs as well as other tissues, is one of COVID-19's most severe side effects. Cancer patients who receive immune-activating therapies including blockers of checkpoints, T-cell therapies of chimeric antigen receptors (CARs), and bi-specific T-cell engagers (BiTEs) are also at threat of health problems if the immune reaction elicited by these strategies attacks natural, safe tissue. Patients who receive CAR T-cell therapies or BiTEs can experience cytokine release disorder, which is close to the cytokine storm shown in COVID-19 victims.  according to the new study, although not completely conclusive, may intensify cytokine discharge syndrome in people receiving such immunotherapies. While patients may be worried about the elevated risk of COVID-19 as a consequence of treating cancer, this does not prevent them from receiving therapy. In certain cases, cancer drugs will extend life and even cure the cancer, it's essential to have in mind the purposes of treatment and to address the costs and benefits of treatment with the psychiatrist in your specific situation (Ziad et al., 2020) .

These viruses are believed to specifically attack the pulmonary part of humans.

COVID-19 is the seventh coronavirus to infect people. COVID-19 is a biologically unique virus in and of itself, and few function of the new corona-virus in tumor has been well revealed so far. Comorbidities including asthma and cancer predispose positive suffers to worse health conditions, comparable to other serious acute respiratory incidents (SARS-CoV-2, MERS-CoV-1) (Yotsana et al., 2020) .

The level of fatalities among COVID-19 cancer victims as a comorbid diagnosis was 7.6%, compared to 3.8% for overall COVID-19 community, as per World Health Organization (WHO) (WHO 2020). As a result, cancer plays a role in COVID-19 pathogenesis. In the United States, upwards of half a million patients are doing treatment, and more than 1.5 million citizens will be in treatment of tumor. Sufferers who are undergoing in action chemotherapy or radiation therapy, or have previously undergone transplantation, are in even greater danger. Even though tumor victims are at a higher threat of serious effects from infection with the SARS-CoV-2 virus, research on COVID-19 in cancer people is still scarce. Immune dysfunction and prolonged inflammation can play a role in COVID-19 positive tumor people's poor results. As a result, it is critical to investigate the root pathways that bind COVID-19 to cancer. A greater awareness of the mechanistic relationship between COVID-19 and cancer would aid in the prevention of infection's harmful consequences as well as the development of new treatments. It's also vital to consider the balance of choosing chemotherapy and antiviral drug therapies, as well as the timing for such treatment.

Chemotherapy must be delayed for some people until antiviral course is completed, whereas some can be exposed to viral disease therapies while receiving antitumor medication (Timothy et al., 2020) .

With regards to the biological interconnection between COVID-19 and cancer, ACE-2, cytokine storm, age, and coagulopathy are a few strong factors that connect COVID-19 and cancer (Borchardt et al., 2014; Vickers et al., 2002) . A deeper understanding of these connecting links may guide us in finding novel anti-viral and anti-cancer therapeutic options (Fig. 2) . ACE-2 is a carboxypeptidase that converts angiotensin-I to angiotensin 1-9, and angiotensin-II to angiotensin 1-7. It has a significant role in cardiac regulation and also has a protective impact in severe lung injury (Zhou et al., 2017) . Similarly, SARS-CoV and SARS-CoV-2 also enter into the human cells via angiotensin 1 ACE-2 (Xu, R., Wani et al., 2020 and Zhu, J., 2019; . The spike protein of the SARS-CoV-2 virus is able to replicate and develop by binding to ACE-2, and being transported together into the cell .

Recent literature suggests that ACE-2 protects mice in contradiction of acute lung injury and avian influenza. Some of the H5N1 infected patients who had higher ACE-2 levels in their blood serum presented well outcomes to avian influenza infection and treating mice with human ACE-2 prevented lung injury (Feng et al., 2011) . Inappropriately, inadequate research work has been done to confirm the mechanistic link between ACE-2 expression and SARS-CoV-2 infection in cancer. Therefore, it would be valuable to test whether levels of ACE-2 increases/decreases in several tissues of cancer patients and COVID-19 infected patients and how this affects COVID-19 infection in these patients. 

In light of these intriguing data sets, it is significant to clarify the relationship between severe COVID-19 as well as preexisting pro-inflammatory and immunosuppressing circumstances associated with cancer ( Fig. 3 ) and its treatments (Tables 1 and 2) . Here, we discuss the common risk factors between severe COVID-19 and cancer. The predisposing factors for cancer are aging, obesity, metabolic syndrome, and exposure to carcinogens. Also, aging, obesity, and metabolic syndrome are represented comorbidities that influence vulnerability to and sternness of SARS-CoV-2 infection. In cancer-infected patients, metastatic spreading and weak Eastern Cooperative Oncology Group (ECOG) performance status also favour COVID sternness (Derosa et al., 2020) .

Aging is one of the utmost common causes, increasing the occurrences of both cancer and SARS-CoV-2 infection, with significantly potential commonalities connecting to immunosenescence, inflammaging (Fig. 3) , and their treatments are presented in Table 2 .

Immunosenescence outlines a status of lessening the function of the body immune systemrelated responses to vaccination, infection, and cancer, also an augmented occurrence of devastating autoimmune diseases in the aging populace (Pawelec, G., 2018) For example, Creactive protein levels are related to ageing CD8 + T cells, plasma blasts as well as granulocytes in ageing persons (Stevenson et al., 2018) Particularly, in patients with COVID-19, lesser T cell counts are related to clinical indicators of inflammation, for example, Ddimers, ferritin, and C-reactive protein, while high quantities of plasma blasts are related to severe disease (Mathew et al., 2020) . Interleukin 6 (IL-6), which has been referred to as the 'gerontologist's cytokine', (Ershler, W.B. and Keller, E.T., 2000) is normally present at low levels in the blood but is increased with aging (Nelke et al., 2019) and correlates with death (Puzianowska-Kuźnicka et al., 2016) . IL-6 is involved in the pathogenesis of numerous chronic ailments, including cancer (Weiss et al., 2013) . The IL-6-JAK-STAT3 pathway is hyperactivated in various types of cancer, driving the propagation, survival, and intrusiveness of cancer cells and suppressing the anti-tumor immune response (Dulos et al., 2012) .

Therefore, tactics directing this pathway have already received US Food and Drug Administration (FDA) approval to treat inflammatory conditions or myeloproliferative neoplasms, and to manage certain adverse effects of chimeric antigen receptor-expressing T cells (CAR T cells) (Johnson et al., 2018) .

Numerous meta-analyses have reported an association between type 2 diabetes (T2D) and cancer, with the strongest relationship found for liver and pancreatic cancer, followed by endometrial cancer (Oberaigner et al., 2014; Dong et al., 2021) . Likewise, severely obese persons with T2D are more probable to become infected by SARS-CoV-2, and are at a higher risk of problems and demise from COVID-19. Interestingly, persons with T2D were also at augmented risk for SARS as well as MERS (Kulcsar et al., 2019) . Related to this, insulin is a vital hormonal garnish of tumor metabolism and development in obesity-related to insulin resistance (Perry, R. J. and Shulman, G.I., 2020) and treatment of T2D during COVID-19 is being instigated to mitigate disease severity (Longo et al., 2020) which may compromise the integrity of the intestinal barrier that located in SARS-CoV-2 replication (Thaiss et al., 2018) .

Through their involvement in immunosurveillance, lymphocytes control the occurrence, development, and therapeutic response of cancers (Galluzzi et al., 2017) . CD4 + and CD8 + T lymphocytes recognize tumor cells expressing immunodominant determinants presented by chief histocompatibility complex class II and class I, respectively. CD4 + lymphopenia, a hallmark of immunosuppressive viral infection, occurs in about 20% of patients with advanced pancreatic cancer, melanoma, non-Hodgkin's lymphoma and breast cancer (Bedimo et al., 2009) .

Lymphopenia regularly escorts cancer diagnosis, treatment, or progression and is a side effect of chemotherapy and steroids. Radiotherapy also decreases lymphocyte counts (Meyer, K.K., 1970 ). An augmented number of blood neutrophils is often combined with reduced lymphocyte counts, resulting from the elevation of the neutrophil-to-lymphocyte ratio. High neutrophil-to-lymphocyte ratio is a poor prognostic indicator and forecasts short cancerspecific progression-free survival after blockade of apoptosis of protein 1 (PD-1), as well as severe COVID-19 (Ocana et al., 2017) 

Investigation have found among defendants, the most common cancer diagnoses were breast cancer (190 patients; 40%), lung cancer (61 patients; 13%), pancreatic cancer (61 patients; 13%), colorectal cancer (41 patients; 8%), hematologic malignancies (31 patients; 6%), gynecologic cancer (24 patients; 5%), prostate cancer (18 patients; 4%), stomach cancer (15 patients; 3%), head and neck cancer (13 patients; 3%), kidney cancer (8 patients; 2%) and other such melanoma, sarcoma and testicular cancer (11 patients; 3%). Overall, in a population characterized by a high level of emotional vulnerability the CoV-19 pandemic had a marginal effect, and only a small percentage of patients stated a rise in their emotional vulnerability ( Fig. 4) (Eva et al., 2021) .

The nationwide lockdown to combat the COVID-19 disease outbreak had a detrimental effect on chemotherapy care, with a substantial decrease in the percentage of people opting for cancer-specific treatment. To minimize the number of hospital visits, the trend of chemotherapy prescriptions shifted to a longer interval and a longer path. Even though COVID-19 new cases were observed in the population, the removal of travel limits increased in numbers of patients seeking advice (Pandey et al., 2020; Wani et al., 2021) .

Anti-viral treatment and opposing his RT-PCR on 2 occasions, a COVID-19 positive people with early phase colon cancer was effectively diagnosed with colectomy without complications (Guilherme et al., 2020). Chinese doctors changed not only the treatment methods for cancer patients but also the medical protocols (Eva et al., 2021) . When it comes to lung cancer, maintaining a high index of suspicion for COVID-19 contamination and safeguarding sensitive patients are top priorities, cancer of the lungs is the much vulnerable type of tumor to COVID-19 contamination, according to three Chinese cohorts. China said that, after the COVID-19 pandemic, China saw a shift in approach in the treatment of oncology people .

Italy was among the first countries to see a dramatic rise in the prevalence and mortality level of COVID-19 cases, by the end of March 2020, there have been over 100,000 incidents and up to 11,600 deaths. Italy quickly protested for a lack of staff, and several oncologists were called in to help with the COVID-19 war. As a result, some areas were converted to only accept COVID-19 patients. Focused on their existing experience, an Italian group of young oncologists proposed several steps to respond to the situation. Several elective operations in colorectal surgery, for example, were restricted in many facilities around the world, but colorectal cancer operations were not included in this policy and continued alongside emergent procedures (Di Saverio et al., 2020) . In the absence of guidelines, few rectal cancer specialists choose to use oral capecitabine instead of 5-FU wherever necessary and to use short-course radiation treatment in the neoadjuvant environment when postponing surgery (De Felice et al., 2020) . A northern Italian association of radiation oncologists suggested an equation that focused on attempting to handle cancer patients with hypo fractionated protocols wherever possible, while withholding or delaying radiation treatment for benign illness, just handle reported or extremely suspect COVID-19 events in the adjuvant environment (Filippi et al., 2020).

Oncology practice in France was similar to China and Italy, but several French organizations currently published standardized recommendations for the treatment of particular cancers. All of these proposals were in line with suggestions made by a panel of French experts commissioned by the leader on March 14th, 2021 the Public Health Council held a meeting to discuss the SARS-CoV-2 virus and solid cancers (You et al., 2020) .

In response to the disease outbreak, cancer clinics around the world implemented procedures like a divided process, prioritizing some subsets of people with cancer for urgent care while delaying treatment for others (Beddok et al., 2020; Wani et al., 2022) . Mauri et al. summarised core recommendations from 63 standards in specialized associations across the planet. Health services are selectively mobilized to the treatment of clinicians with COVID-19 in hospitals servicing communities with a heavy caseload of SARS-CoV-2 disease, including New Delhi, Mumbai, Milan, Madrid, and New York, possibly jeopardizing normal operations like cancer testing and treatment (Mauri et al., 2020) .

Since the pandemic, another problem that doctors caring for is deciding which systemic care is best for the metastatic tumor people have had from the various options available, particularly in light of new evidence that hospital entry or repeated hospital visits could be possible causes for cancer sufferers contracting the SARS-CoV-2 virus. People with this disease in low-income and middle-income countries have faced increasingly daunting difficulties (Trehan, H.S., and Vijay, S.K., 2021) . During this pandemic, guidelines support the utilization of regimens with reduced levels of cytopenia in the area of genitourinary cancers, where various therapeutic methods such as chemotherapy, selective treatments, hormonal therapies, immunotherapeutic, or radionuclides may be provided to patients (Gillessen, S., and Thomas, P., 2020) .

A recent study demonstrates that some patients with cancer face a higher risk of death if affected by COVID-19, which is predominantly driven by older age, smoking, the presence of active disease and associated risk factors. Patients who are otherwise healthy and have Our data endorse the recommendations to minimize the risk of SARS-CoV-2 infection in patients with cancer with active preventive measures, especially in subgroups of patients with recognized poor prognostic factors, and to perform close monitoring in the case of exposure to the virus or COVID-19 related symptoms. The mortality data from selected studies on patients with cancer and COVID-19 are presented in Table 1 . Genetic studies: Vitamin D receptor gene (VDR) alleles associated with increased susceptibility to respiratory or viral infections (Jolliffe et al., 2018) Ab, antibody; ADT, androgen deprivation therapy; ARDS, acute respiratory distress syndrome; CML, chronic myeloid leukemia; CLL, chronic lymphocytic leukemia; EBV, Epstein-Barr virus; EMA, European Medical Agency; GVHD, graft-versus-host disease; HCC, hepatocarcinoma; HLH, hemophagocytic lymphohistiocytosis; iNOS, inducible nitric acid synthase; NSCLC, non-small-cell lung cancer; poly-ICLC, polyinosinic-polycytidylic acid; RCC, renal-cell carcinoma. (Saleem et al., 2012) Melanoma (Hall et al., 2018) In humans: Phase 1 trial in melanoma, glioblastoma and myeloma (Saleem et al., 2012) Autophagy inhibition (Levy et al., 2017) Akt signaling pathway inhibition G2/M cell cycle arrest (Jiang et al 2008) Increase in CTL Response (Xu et al., 2014) Primary effusion lymphoma cells (Kariya et al., 2014) Melanoma cells (Paskas et al., 2019) Lymphoblastic and myeloid leukemia Cells (Maksimovic et al., 2015) In mice: Prostate cancer Colon cancer (Selvakumaran et al., 2013) Caspase-dependent Apoptosis (Kariya et al., 2014) Suppression of NF-κB activity by inhibition of KK phosphorylation in PEL cells (Kariya et al., 2014) Inhibition of proliferation, Transient activation of Akt and inhibition of P70 S6 kinase (Paskas et al., 2019) ER stress Cell signaling induction, including Akt and mTOR (Meier et al., 2017) No Nitazoxanide Giardia lamblia diarrhea; Cryptosporidium parvum diarrhea Yes (Anastasiou et al., 2020) Glioblastoma cells In mice: CRC (Senkowski et al., 2015) G1-phase cell cycle arrest, inhibition of protein translation via the mTOR-c-Myc-p27 pathway (Ripani et al., 2020) (Haruki et al., 2013) Pancreatic Cancer (Gocho et al., 2013) family members (Iwase et al., 2013) Oseltamivir

Limited (Srinivas et al., 2020) BC cells (Thulasiraman et al., 2019) In canines and mice: Increase mammary tumor aggressiveness (deOliveira et al., 2015) Increase of cleaved caspase 3 expression (Thulasiraman et al., 2019) No

Yes (Hongyan et al., 2020) Oral hairy Leukoplakia (Moura et al., 2010) No Accumulation of cells in S phase and apoptotic death (Shaw et al., 2001) (Ikezoe et al., 2004) In humans: Glioma-no Efficacy (Laurent et al., 2004) Suppression of pro-survival BCL-2 family member and 

No Yes No

BC, breast cancer; BCL-2, B cell lymphoma 2; CLL, chronic lymphocytic leukemia; COPD, chronic obstructive pulmonary disease; CTL, cytotoxic T lymphocytes; CRC, colorectal cancer; eIF4E, eukaryotic initiation factor 4; ERK, extracellular signal-regulated kinase; EZH2, enhancer of zeste homolog 2; GC, gastric cancer; HCC, hepatocellular carcinoma; HNSCC, head and neck squamous-cell carcinoma; HPV, human papillomavirus; IL, interleukin; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor-κB; NSCLC, non-small-cell lung cancer; RCC, renal-cell carcinoma; SCC, squamous-cell carcinoma; STAT1, signal transducers and activators of transcription protein; TNF-α, tumor necrosis factor-α; VEGF, vascular endothelial growth factor.

The most important symptomatic treatment for COVID-19 patients is oxygen therapy . For cancer patients with COVID-19, there was a higher percentage of patients who received oxygen therapy . The higher proportion of COVID-19 patients with cancer requiring oxygen therapy and mechanical ventilation may be related to more severe disease and an immunosuppressive state in cancer patients, who are more susceptible to secondary lung infection with other pathogens.

Currently, there is no antiviral drug that is specifically effective against SARS-CoV-2.

Several clinical studies have indicated that remdsivir, arbidol, and chloroquine may have moderate benefits for treating COVID-19 Grein et al., 2020) . Larger clinical studies need to confirm these results. For cancer patients with COVID-19, the use of antiviral drugs did not yield any different outcomes compared with general COVID-19

patients. About 71.4% of cancer patients with COVID-19 received at least one antiviral agent, including arbidol, lopinavir/ritonavir, ganciclovir, and ribavirin, while 32.1% received two or more antiviral agents Dai et al., 2020) .

Given that COVID-19 cancer patients may have systemic immunosuppression, intravenous immunoglobulin may be a promising treatment of COVID-19. One study showed that 12 out of 28 cancer patients with COVID-19 received intravenous immunoglobulin treatment. However, the study could not provide adequate information about efficacy due to the limited sample size and lack of a randomized control group .

The rationale for anti-inflammatory therapy is based on the premise that COVID-19 induces a cytokine storm with deleterious effects on tissues (Tobaiqy et al., 2020) . In a controlled, open-label trial, the use of dexamethasone in hospitalized patients with COVID-19 resulted in lower 28-day mortality among those receiving either invasive mechanical ventilation or oxygen alone (Horby et al., 2020) . For cancer patients with COVID-19, the use of systemic corticosteroids remains controversial. Given that cancer patients are already at a higher risk of opportunistic infections, the use of corticosteroids may not be effective in mitigating COVID-19 symptoms. Indeed, one study showed that corticosteroids did not reduce the incidence of severe events in cancer patients with COVID-19 . Blood purification therapy is an alternative treatment to reduce cytokine storms and benefit critically ill COVID-19 patients. One report showed that the therapy was effective in managing cytokine storms and pathogenic antibodies in three critically ill COVID-19 patients with profound inflammations . However, larger randomized data were lacking.

Furthermore, multi-disciplinary efforts are needed to achieve increased availability of blood purification therapy for COVID-19 cancer patients.

Convalescent plasma therapy has also been explored to alleviate COVID-19 symptoms (Tobaiqy et al., 2020) . Of note, there are some potential risks and ethical issues associated with its usage, including thrombotic risk and the selection of donors. Given that cancer patients with COVID-19 may have a more rapid disease progression, convalescent plasma therapy may be particularly beneficial in this population. To date, there is no report about the effectiveness of convalescent plasma therapy in this patient population.

It is known that immune tolerance is a key part of tumorigenesis and anti-tumor therapy resistance (Dong et al., 2020) . Similar to cancer therapy, one method of vaccine development may be a T cell epitope vaccine to enhance the T cell recognition of virus-infected cells. The regimen used to prevent or reduce the cytokine storm in cancer patients during CAR-T cell therapy may also be used to reduce the risk of cytokine storm in COVID-19 patients. It is known that IL-6 is a critical cytokine involved in cancer and inflammation. High levels of IL-6 predict poor prognoses of patients with COVID-19 (Zhao et al., 2020) . Among 129 patients hospitalized for COVID-19, those who received tocilizumab in addition to standard treatment were significantly less likely to need ventilation or die within 2 weeks, when compared with those who received standard treatment alone. Therefore, antibodies targeting the IL-6 receptor (tocilizumab and sarilumab), IL-6 (siltuximab),and other receptor antagonists (α1adrenergic receptor antagonist, prazosin) for mitigating cytokine storm are promising therapeutic strategies for the treatment of cancer patients with COVID-19 (Konig et al., 2020) . Besides IL-6, other cytokines such as type-I interferon, IL-1β, IL-7, IL-17, and TNF-α are central to the pathophysiology of COVID-19 (Jamilloux et al., 2020) . In particular, IL-17 is a critical cytokine associated with immune responses in both cancer and COVID-19

patients (Cafarotti et al., 2020) . Given that anti-IL-17 antibodies have demonstrated a therapeutic role in the treatment of cancer and lung infection by H1N1 and AIDS41, this approach might be useful to control COVID-19 in cancer patients.

Despite all of the attempts, identifying the best solution for people with cancer in the face of the COVID-19 challenge is proving difficult. Assumed the doubts about the benefits of PD-1 and/or PD-L1/IL-6R antagonist , other options are being examined i.e. passive transfer of neutralizing anti-SARS-CoV-2 antibodies for weak patients at a mild to the serious phase of COVID-19 (Hansen et al., 2020) . Lastly, active vaccination will be a greater choice for patients to get rid of the high risk of evolving severe COVID-19 nonetheless still capable of rising defensive anti-viral Tcell responses (Weiss et al., 2013) .

However, to evaluate their efficacy and safety coronavirus vaccines will have to undergo worldwide large-scale phase-3 clinical trials. All these possibilities need urgent investigation to permit clinical oncologists to steer between cancer and COVID-19 in complete obedience with the Hippocratic Oath: primum non nocere-first, not harm.

Beyondthe clinical assumptions, oncologists must keep in mind that if the COVID-19 epidemic spread, the possibility of raised cancer therapy being unavailable is larger than the risk of a SARS-CoV-2 ailment in a cancer victim.

Not Applicable.

All data of this paper will be available on request.

Nil.

All authors of this manuscript declared that no conflict of interest exists Ester di, G., Giuseppe, B., Gianluca, P., Stefano, S., Fabrizia, C., Giovanni de, G., Massimo, C., 2020. Management of older people during the COVID-19 outbreak: Guo, C., Bin, L., Huan, M., 2020. Single-cell analysis of two severe COVID-19 patients reveals a monocyte-associated and tocilizumab-responding cytokine storm. Nat.

Commun. 11, 1-11. https://doi.org/10.1038/s41467-020-17834-w. 

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We thank the University of Science and Technology Meghalaya, Ri-Bhoi, India and Dean Research, University of Kashmir, Srinagar, India.

Shahid Ud Din Wani, https://orcid.org/0000-0001-9860-0124

Nil.We, the undersigning authors declare that this manuscript is original, has not been published before and is not currently being considered for publication elsewhere.We confirm that the manuscript has been read and approved by all named authors and that there are no other persons, who satisfied the criteria for authorship, but are not listed.We further confirm that the order of authors listed in the manuscript has been approved by all of us.We understand that the Corresponding Author is the sole contact for the editorial process.He is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs.We the undersigned agree with all of the above.

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